(spoilers, but not really, because Shonda will kill them all in the end, despite their weeping and clawing at life)
Meredith Grey: Meredith's mother, who was a chilly and neglectful parent, has Alzheimer's. Meredith falls in love with a handsome surgeon, Derek, who breaks her heart when he reveals that he has a very beautiful wife, Addison, who is an even better surgeon. Meredith has an unsatisfying reunion with her father, Thatcher, who has a new and better family now. Meredith acts out by sleeping with her friend George, but cries during sex and breaks his heart. Meredith's dog dies. Meredith falls briefly in love with a bomb technician, but he gets blown up. Meredith's mother briefly regains lucidity, just in time to tell Meredith what a disappointment she is as a surgeon. Meredith falls off a pier and nearly dies. Meredith wakes up to discover that her mother is dead. Meredith and Derek get back together. Meredith and Derek break up. Meredith and Derek are supposed to get married, but postpone it because their friend has a terminal brain tumor. Meredith's father's new wife dies, he blames Meredith and becomes an alcoholic. Meredith gives him part of her liver. Meredith has a miscarriage. Meredith has a "hostile uterus." Meredith is caught tampering with an Alzheimer's trial. Meredith is fired. Meredith has her adopted baby briefly taken away. Meredith watches her sister, who she now loves, die in a gruesome plane crash and cannot save her.
Cristina Yang: Cristina nearly dies from an ectopic pregnancy. Cristina's lover is shot in the arm, impeding his ability to be a surgeon. Cristina helps him cover it up, confesses, he breaks up with her. Cristina and her lover reunite, they plan a wedding, she does not want to get married. Cristina's lover leaves her at the altar. Cristina is injured by a falling icicle. Cristina begins dating and eventually marries a doctor with PTSD who tries to strangle her in his sleep. Cristina herself develops PTSD following a second hospital shooting and can no longer operate. Cristina is tricked into operating on her mentor's husband, who dies. Cristina has an abortion, which tears her marriage apart. Cristina's husband cheats on her. Cristina is in a gruesome plane crash and develops brief reactive psychosis.
Richard Webber: Richard's wife leaves him. Richard's ex-lover dies of Alzheimer's. Richard's wife miscarries his baby. Richard and his wife reunite and then separate. Richard starts drinking again. Richard and his wife reunite. Richard's wife develops Alzheimer's. Richard steps down as Chief of Surgery. Richard puts his wife in a home. Richard's wife falls in love with someone else.
Derek Shepherd: Derek gets a divorce. Derek is sued for malpractice and becomes seriously depressed. Derek is shot and his girlfriend miscarries. Derek's father dies. Derek's new wife screws up his clinical trial. Derek is in a plane crash and his hand is mangled. Derek undergoes surgery to regain greater function, but his hand goes numb the first time he tries to operate.
Izzie Stevens: Izzie's boyfriend can't deal with her job, and dumps her. Izzie is taunted for being a former underwear model. Izzie's new boyfriend cheats on her. Izzie falls in love with a patient and destroys her career trying to save him, but he dies anyway. Izzie had given up a daughter for adoption as a teenager, Izzie's daughter arrives at the hospital suffering from leukemia. Izzie gives her some bone marrow. Izzie helps destroy her friend's marriage only to discover she and her friend are not sexually compatible. Izzie thinks she is seeing a ghost, but, in fact, has Stage IV metastatic melanoma which has spread to her brain. Izzie gets fired. Izzie's husband asks for a divorce.
Alex Karev: Alex gets syphilis. Alex fails his medical board exams. Alex experiences erectile dysfunction. Alex's girlfriend breaks up with him, they get back together, she dumps him for a dying patient. Alex falls in love with a different patient, but she eventually regains her memory and goes back to her husband and comes back and tells him she's pregnant but she's not really pregnant, just mentally ill. Alex and his girlfriend get back together, but then she discovers she has cancer. Alex and his girlfriend get married anyway, but then she gets fired and they break up. Alex gets shot by a patient's husband. Alex falls in love with someone new and turns down a job opportunity for her, which she then takes for herself, leaving him. Alex has to amputate his mentor's leg against her will. Alex's mentor blames him for everything.
George O'Malley: George kills his first patient. George gets syphilis. George has his heart broken by Meredith. George fails his intern exams. George's father dies of cancer and a leaking aortic valve. George elopes due to grief, cheats on his wife immediately, leaves her for another woman, breaks up with the other woman. George is hit by a bus, horribly disfigured, and then dies.
Miranda Bailey: Miranda gives birth during a bomb scare without her husband, who was in a car accident. Miranda loses out on being Chief Resident. Miranda's son pulls a bookcase on himself and almost dies. Miranda's husband can't handle her schedule and blames her for the accident, they get a divorce. Miranda is trapped during a hospital shooting and has a friend die in her arms. Miranda suffers from PTSD following the incident.
Mark Sloan: Dead.
Lexie Grey: Dead.
Arizona Robbins: Lost leg.
Teddy Altman: Dead husband.
April Kepner: Lost virginity, went nuts, failed boards.